The brain contains all messenger RNA species encoding the five known subtypes of muscarinic receptors. These receptor subtypes have been classified into two general groups according to their preferential coupling to various signal transduction pathways. The M1, M3 and M5 receptors are known to couple to phospholipase C via the G protein subtype, Gq, while the M2 and M4 receptors preferentially couple to inhibition of adenylyl cyclase through t he inhibitory G protein, Gi. However, more careful investigation of this broad functional classification is required. This will lead to a better understanding of the physiological roles of these receptor subtypes in the regulation of neuronal function. Discernment of the functional roles of M2 and M4 muscarinic receptor subtypes is highly relevant, since these two receptors are predominantly localized presynaptically and they play an important role in modulation of acetylcholine release. Unfolding potential differential coupling of these two receptor subtypes to signaling pathways might lead to the development of pharmacological agents that would enhance cholinergic neurotransmission. These agents would have therapeutic potential in Alzheimer's disease.